Voltage-dependent activation of Rac1 by Nav 1.5 channels promotes cell migration.
J Cell Physiol
; 235(4): 3950-3972, 2020 04.
Article
em En
| MEDLINE
| ID: mdl-31612502
ABSTRACT
Ion channels can regulate the plasma membrane potential (Vm ) and cell migration as a result of altered ion flux. However, the mechanism by which Vm regulates motility remains unclear. Here, we show that the Nav 1.5 sodium channel carries persistent inward Na+ current which depolarizes the resting Vm at the timescale of minutes. This Nav 1.5-dependent Vm depolarization increases Rac1 colocalization with phosphatidylserine, to which it is anchored at the leading edge of migrating cells, promoting Rac1 activation. A genetically encoded FRET biosensor of Rac1 activation shows that depolarization-induced Rac1 activation results in acquisition of a motile phenotype. By identifying Nav 1.5-mediated Vm depolarization as a regulator of Rac1 activation, we link ionic and electrical signaling at the plasma membrane to small GTPase-dependent cytoskeletal reorganization and cellular migration. We uncover a novel and unexpected mechanism for Rac1 activation, which fine tunes cell migration in response to ionic and/or electric field changes in the local microenvironment.
Palavras-chave
Texto completo:
1
Bases de dados:
MEDLINE
Assunto principal:
Neoplasias da Mama
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Proteínas rac1 de Ligação ao GTP
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Microambiente Celular
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Canal de Sódio Disparado por Voltagem NAV1.5
Limite:
Female
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Humans
Idioma:
En
Revista:
J Cell Physiol
Ano de publicação:
2020
Tipo de documento:
Article
País de afiliação:
Reino Unido